Human breast cancer: identification of populations with a high risk of early relapse in relation to both oestrogen receptor status and c-erbB-2 overexpression

Abstract

Summary We recently defined a new early prognostic factor, the ER+(R) status, which permits the discrimination of a group presenting a high risk of early relapse among the ER' patients. This group was referred to as ER+(R2) in contrast to ER+(R1) which corresponded to the group of ER' patients having a lower risk of early relapse. Taking into account the whole population including the ER-and inflammatory tumours, we have extended this view and showed that ER+(R) status is a significant predictor of disease-free survival. Determination of c-erbB-2 mRNA levels in the same series of tumours showed that high expression of c-erbB-2 mRNA is significantly correlated with ER-, inflammatory tumours and with lymph nodes involvement. Moreover, a multivariate analysis showed that c-erbB-2 mRNA overexpression was a significant predictor of early relapse (P=0.02), as significant as ER negativity and ER+(R2). For ER' patients a high level of c-erbB-2 mRNA constitutes a higher risk of relapse for both ER+(RI) and ER+(R2) patients. However, in the case of ER-patients, early relapses were strongly correlated with c-erbB-2 overexpression. The counterpart of this observation is that ER-patients with no overexpression of c-erbB-2 constitute a group with a relatively good prognosis.Management of breast cancer treatment depends on a good knowledge of the prognostic factors enabling the identification of patients with either a low or high risk of recurrence. A knowledge of the steroid receptor status, specifically the oestrogen receptor (ER), should allow the prediction of the response to hormonal therapy and to some extent disease-free survival, site of relapse and overall survival (Knight et al., 1977;Pichon et al., 1980;Clark et al., 1983;Allegra et al., 1979;Blanco et al., 1984;Fisher et al., 1983;Hahnel et al., 1979;Saez et al., 1983). Although there is a general agreement on the higher risk of relapse for receptornegative (ER-) patients, the prognostic value of ER status is not accepted by all authors (Aamdal et al., 1984;Howell et al., 1984; Felman et al., 1986;Parl et al., 1984). Among ER-positive (ER') patients regarded as having a more favourable prognosis, we have recently defined a group presenting a high risk of relapse (May et al., 1989). This group of patients, called ER+(R2), has been characterised by a ratio of (ER-protein in fmol per mg total proteins) to (ERmRNA in pg per 4pg total RNA) higher than 1.5. According to these results, ER+(R) status has been assigned as an early prognostic factor.On the other hand, amplification of the c-erbB-2 gene is an alteration frequently associated with breast cancer. This gene encodes a transmembrane protein that shows extensive homology with the receptor for epidermal growth factor (Coussens et al., 1985;Bargmann et al., 1986;Yamamoto et al., 1986), indicating that c-erbB-2 is a membrane-bound receptor. A ligand for c-erbB-2, however, has not yet been identified. A number of studies regarding amplification of this gene in primary human breast cancer has been published (see Table I...

Immunohistochemical evaluation of human epidermal growth factor receptor 2 and estrogen and progesterone receptors in breast carcinoma in Jordan

“…These figures are also in agreement with data reported in the literature [38,43,49]. Our data also show a strong inverse correlation between Her-2 and ER expression, which is in agreement with data reported by others [10,39,50,51]. Unlike reported data that shows a correlation between ER expression and tumor grade [41,43,47,49], however, we were unable to confirm such a correlation in our cases.…”

SHP2 is up‐regulated in breast cancer cells and in infiltrating ductal carcinoma of the breast, implying its involvement in breast oncogenesis

“…Consistent with previous reports that HER2− tumours tend to be ERα/PR+, 49–51 33 of the 45 tumours in this group were positive for these hormone receptors (Tables S1B and 2B). Our results show that the incidence of SHP2 overexpression in HER2−, but ERα/PR+ tumours was 79% (Table 2B), suggesting a positive relationship between SHP2 overexpression and nuclear accumulation of ERα/PR.…”

c-erbB-2 oncogene as a prognostic marker in breast cancer

“…The results of these studies have varied considerably but several studies have found consistent results with respect to certain prognostic factors. The original study reported by Slamon et al (1987) showed a positive association between c-erbB-2 expression and the number of involved axillary nodes, this finding has not been generally reproducible but finds some support in three other studies (Tandon et al, 1989;Guerin et al, 1989;May et al, 1990) and indirectly in the study by Zhou et al (1989) ship between c-erbB-2 expression and other markers of differentiation. Ploidy has previously been investigated by two groups neither of whom found any significant association (Tavassoli et al, 1989;Ro et al, 1989) At least 20 other groups have now published data concerning the prognostic significance of c-erbB-2, of these only four groups have failed to find a prognostic effect of c-erbB-2 in at least one sub group (Zhou et al, 1989;Ali et al, 1988;Gusterson et al, 1988;Barnes et al, 1988).…”

“…Wright et al (1989a) also found that the prognostic effect of c-erbB-2 expression was stronger in ER positive than ER negative tumours and also stronger in EGFR negative tumours than EGFR positive tumours. May et al (1989) (May et al, 1990) c-erbB-2 receptor expression is equivalent in node positive and in node negative patients and make the extremely important point that in order to reliably demonstrate the prognostic effect of c-erbB-2 expression in the node negative subset large numbers of patients are required. This is because c-erbB-2 is expressed relatively infrequently and because node negative patients have a much better prognosis than node positive patients and therefore relapse and die less frequently.…”